The molecular mechanisms of iron uptake have been studied. We have explained the unique transferrin cycle in terms of the specific interactions of transferrin with its receptor as a function of both pH and iron saturation. The recycling of transferrin during endocytosis has been compared and contrasted with the classical endocytic pathway in liver taken by asialoglycoproteins. We have developed quantitative intracellular assays to determine the timing, site and mechanisms involved in sorting and routing of ligand and receptor. We have demonstrated the biosynthetic regulation of the transferrin receptor by intracellular iron and are currently elucidating the mechanisms behind this. The routing of intrinsic membrane proteins has been studied using Herpes Simplex Virus glycoproteins. These studies have established this system as one that provides a model for the sorting of intrinsic proteins of the nuclear membrane. Our findings demonstrate the rapid and complete sorting during or immediately after biosynthesis thus ruling out the role of the Golgi and post translational modifications in this process for the nuclear membrane. The relationship of organelle movement location and traffic to the cytoskeleton lies at the heart of intracellular pathways. We have demonstrated that the Golgi apparatus is localized by the microtubule system and the utility of the technique of microinjection of monoclonal antibodies into living cells to perturb cytoskeletal-organelle interactions. We have raised monoclonal antibodies against integral membrane proteins of the Golgi and the microtubule system to define further the individual proteins that determine specific and localized cytoskeletal interactions in the cell.